Odronextamab Demonstrates High Complete Response Rates in Relapsed/Refractory Follicular Lymphoma

Odronextamab Demonstrates High Complete Response Rates in Relapsed/Refractory Follicular Lymphoma

Odronextamab contributed to high complete response rates with a manageable safety profile in patients with heavily pretreated relapsed/refractory follicular lymphoma, as demonstrated by findings from a study published in the Annals of Oncology.

In the ELM-2 study (NCT03888105), among 128 patients with relapsed/refractory follicular lymphoma after 2 or more lines of systemic therapy, treatment with odronextamab elicited an objective response rate (ORR) of 80.0% (95% CI, 72.5%-86.9%) at 20.1 months of efficacy follow-up. The complete response (CR) rate in this study was 73.4%. Patients had a median duration of CR of 25.1 months (95% CI, 20.5-not evaluable [NE]). The probability of patients maintaining CR for 12 months was 75.0%.

The median progression-free survival (PFS) was 20.7 months. In addition, the rate of 12-month PFS was 66.2%, 18-month PFS was 57.5%, and 24-month PFS was 46.1%. Median overall survival (OS) was not reached during the study, with a 12-month OS rate of 86.2% and a 24-month OS rate of 70.1%. Compared with patients with a partial response to treatment, those with a complete response to treatment had a great median PFS (27.8 months vs 11.3 months) and median OS (not reached vs 18.4 months).

Sixteen percent of patients treated with odronextamab discontinued treatment due to adverse events (AEs). The most common treatment-emergent AEs that occurred during the study were cytokine release syndrome (CRS; 56%), pyrexia (38%), and neutropenia (38%).

“In this study, odronextamab treatment achieved deep and durable responses in heavily pretreated patients with [relapsed/refractory follicular lymphoma] and demonstrated a generally manageable safety profile,” the study authors wrote. “These data are consistent with those from patients with [relapsed/refractory follicular lymphoma] in the ELM-1 study and with results reported in patients with [relapsed/refractory] diffuse large B-cell lymphoma, supporting the potential of odronextamab for management of indolent and aggressive B-NHL.”

In this phase 2, open-label, multicohort, multicenter study, researchers included patients aged 18 years and older with grade 1-3a follicular lymphoma whose disease was refractory to or relapsed after 2 or more prior lines of systemic therapy, including an anti-CD20 antibody and alkylator. Patients also must have either been considered unsuitable or failed treatment with rituximab plus lenalidomide, and had measurable disease. Additionally, patients had an Eastern Cooperative Oncology performance status between 0 and 1, adequate bone marrow, and hepatic and renal function.

Patients were treated with intravenous odronextamab during 21-day cycles. Step-up dosing was utilized in cycle 1 to help mitigate risks for CRS, followed by 80 mg of odronextamab on day 1, 8, and 15 during cycles 2 to 4. A maintenance dose of odronextamab at 160 mg was also given to patients every 2 weeks, which continued until disease progression or another reason for treatment discontinuation. The dosing frequency was reduced to 160 mg every 4 weeks for patients with CR lasting at least 9 months.

The primary endpoint of this study was ORR based on best overall response and was assessed at week 12 by independent central review per Lugano criteria. Secondary endpoints of the study included ORR per local investigator, the rate of CR, duration of response, OS, PFS, patient-reported outcomes, and pharmacokinetics. Minimal residual disease status and CD20 expression were exploratory endpoints in the study.

“This study has demonstrated the compelling, durable efficacy and generally manageable safety of odronextamab in [relapsed/refractory follicular lymphoma],” the study authors concluded. “These results support further investigation of odronextamab in FL, as monotherapy and in combination with other agents. Phase III trials of odronextamab in the earlier-line setting are ongoing.”

Reference

Kim TM, Taszner M, Novelli S, et al. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma. Ann Oncol. Published online August 13, 2024. doi:10.1016/j.annonc.2024.08.2239